Progress 09/01/17 to 08/31/21
Outputs
Target Audience:The target audience includes dairy producers, other researchers, animal scientists, extension specialists, students, veterinarians, industry stakeholders and regulatory representatives. Bloomberg Businessweek: This Genetics Company Is Editing Horns Off Milk Cows 10/12/2017 Science Friction (ABC radio Australia): Making happier animals? Gene editing on the farmyard 11/17/2017 Successful Farming: Cattle Geneticist and Active Spokesperson for Ag 11/23/2017 Genetic Literacy Project: Geneticist Alison Van Eenennaam: Genetic engineering could save farm animals from disease 11/29/2017 Pacific Standard Magazine: Why the FDA's Plan to Regulate Gene Editing in Animals Has Some Scientists Worried 11/1/2018 Synthego Podcast: Alison Van Eenennaam Edits Cattle Using CRISPR 12/4/2018 Washington Post: Gene-edited farm animals are coming. Will we eat them? 12/17/2018 Dairy Herd Management: Gene Editing finds its Way to the Farm 12/21/2018 Flash Forward Podcast: Snip snip snip 12/18/2018 The Conversation: Gene-edited food regulations: whether it's a plant or animal shouldn't matter, but it does now 2/26/2019 The Daily Beast: Is a Gene-Edited Animal a Drug? 2/27/2019 Genetic Literacy Project Podcast: US researchers moving abroad to avoid FDA's CRISPR-edited animal regulations 3/14/2019 Futurism.com: Scientists Are Fleeing America's Rules About Gene-Editing Animals 3/15/2019 Wired: A more human livestock industry, brought to you by CRISPR 3/19/2019 Genetic Literacy Project Viewpoint: FDA plan to regulate gene-edited animals as drugs will thwart US food innovation 4/8/2019 Pacific Standard: AMERICA'S LEADING ANIMAL GENETICIST WANTS TO TALK TO YOU ABOUT GMOS 4/18/2019 Genetic Literacy Project Viewpoint: "300 scientists say FDA's plan to regulate CRISPR-edited animals as drugs will effectively shut down innovation" 4/30/2019 SPLASH Milk Science Update: Genetic Editing Eliminates Dairy Cattle Horns 5/1/2019 Farmers Weekly: Livestock gene editing: Current rules and potential benefits 6/4/2019 DTN Progressive Famer: "Edit FDA regulation for Genes" 6/25/2019 Feedstuffs Foodlink: "Current U.S. gene editing regulatory framework lags" 6/25/2019 Farm Journal PORK magazine: "NPPC Campaign Broadens Awareness of Gene Editing's Promise" 6/25/2019 AgNet West: Industry Concerned with FDA Oversight of Animal Genomics 6/26/2019 Ohio Ag Net: Edit FDA Regulation for Genes 6/27/2019 Nebraska Corn Board CornsTalk "Food Innovation: GMOs, CRISPR and beyond": Improving Animals through Genetic Innovation" 7/1/2019 WATTAgNet.com: Gene editing could alleviate ASF's impact on industry 7/3/2019 High Plains Journal: NPPC stresses importance of keeping up with technology 7/9/2019 Podcast: Dr. Alison Van Eenennaam-Animal Genetics, Food Marketing, and World Hunger 7/28/2019 Technology Networks: Grabbing the horns from the bull 8/5/2019 Wired: We're eating this planet to death 8/8/2019 AgriNews: U.S. approval process for gene-edited livestock may hamper research 8/26/2019 Technology Networks: Technology Networks Explores the CRISPR Revolution 9/20/2019 Hoards Dairyman: DCRC Annual Meeting: Genome Editing in Cattle 10/1/2019 UC Davis News: Genome-Edited Bull Passes on Hornless Trait to Calves 10/7/2019 BBC News: Genome-Edited Bull Passes Hornless Gene to Calves 10/7/2019 Grist: Gene editing could help save the planet-if scientists can avoid the typos 10/7/2019 Discover Magazine: Scientists Used Gene Editing to Create a Bull Without Horns. It Passed the Trait to its Offspring 10/7/2019 Sky News: DNA editing sees horned bull father six hornless calves 10/7/2019 Mirror: Horned bull genetically edited by scientists becomes 'dad' to six hornless calves 10/7/2019 Eurek Alert!: Genome-edited bull passes on hornless trait to calves10/7/2019 The Telegraph: Bulls genetically engineered without horns to stop farmers and walkers being gored 10/7/2019 Daily Democrat: UC Davis breeds bull without horns 10/7/2019 The Sun: BULL THE OTHER ONE. Mutant bulls without horns created in gene-editing experiment 10/7/2019 Phys.org: Genome-edited bull passes on hornless trait to calves 10/7/2019 UC Davis Unfold Podcast: Episode 4 The Future of Food 10/8/2019 Wired: A Cow, a Controversy, and a Dashed Dream of More Humane Farms 10/8/2019 Genetic Engineering and Biotechnology News: Hornless Genome-Edited Bull Passes Trait to Offspring 10/8/2019 AgroPortal: Offspring of gene-edited, hornless dairy bull born healthy, study confirms 10/8/2019 GenomeWeb: Calves from hornless cattle 10/8/2019 FirstPost: Gene-edited hornless cattle meat does not get FDA approvcal for human consumption 10/8/2019 The Mice Times of Asia: Without horns: scientists have deduced new breed of the bulls 10/8/2019 FarmingUK: Scientists genetically engineer hornless dairy bulls 10/9/2019 The Standard: Getting gene-edits from stable to table 10/10/2019 California Dairy Magazine: Genome-Edited Bull Passes on Hornless Trait to Calves 10/10/2019 California Ag Network: Genome-Edited Bull Passes on Hornless Trait to Calves 10/10/2019 Associated Press: Gene-edited livestock carry huge promise but major pitfalls 10/12/2019 The Burn-In: Gene-hacking scientists create bulls with no horns 10/14/2019 AgNet West: Preventing Horn Growth in Dairy Cows Through Genome Editing 10/16/2019 Beef Magazine: Accelerated genetic progress 10/16/2019 ISAAA: Hornless Cattle Now Possible Thanks to Genome-editing 10/16/2019 The Western Producer: Scientists use gene editing to produce hornless calves 10/17/2019 Texas Standard: Researchers Use Genome Editing To Breed Hornless Cattle 10/21/2019 Singularity Hub: CRISPR Just Created a Hornless Bull, and It's a Step Forward for Gene-Edited Food 10/22/2019 Genetic Literacy Project: Netflix `Unnatural Selection' gene editing miniseries focuses on extreme examples, ignores potential food sustainability impact of CRISPR 10/23/2019 Progressive Cattle: Gene editing: Does it have a place in the future of beef? 10/24/2019 That'sFarming: Bull genetically edited to produce hornless calves 10/27/2019 Capitol Press: Gene-edited food is coming, but will shoppers buy? 11/14/2019 Technology Networks: Technology Networks Explores the CRISPR Revolution: An Interview With Livestock Geneticist Alison Van Eenennaam Genetic Literacy Project: Geneticist Alison Van Eenennaam explains how the CRISPR gene editing `revolution' can improve our food AgriPulse: FDA: New analysis backs tough regulatory approach to biotech animals 2/7/2020 ABC National Radio Background Briefing: Mutants or miracles? Australia's GM cows 3/15/2020 ABC Television: Landline: GM cows: Genetically modifying dairy cattle 3/15/2020 ABC National Radio AM: "No big deal": modified cattle in Victoria carried genetic contamination 3/14/2020 Genetic literacy project: Video: What are the risks and benefits of animal gene editing? 8/17/20 Genetic Literacy Project: GE animals: While the federal government delays approvals, antibiotic use, animal suffering and food prices increase 1/11/21 Genetic Literacy Project: Viewpoint: 'Regulatory creep'--How the FDA's evolving rules hindered the introduction of gene-edited animals 1/13/21 Forbes: FDA and USDA Spar Over Genetically-Engineered Animals 1/15/21 Genetic Literacy Project: 'Back to the future': The case for returning some animal biotech oversight to the USDA 1/15/21 Nature World News: FDA or USDA: Who Should Oversee the Regulation of Genetically-Engineered Animals? 1/16/21 Genetic Literacy Project Podcast: FDA's double standard? Geneticist Alison Van Eenennaam examines why agency defends GE crops but overregulates GE animals 2/3/21 Ag Information Network: Gene Editing for Animal Welfare 4/13/21 Ag Information Network: Gene Editing for Animal Welfare - Part Two 4/14/21 Dairy Herd Management: The Fast Track to Polled Genetics 7/8/21 Drovers: Gene Editing in Today's Beef Industry and the Future 10/20/21 Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?The animals have served as educational and training examples for a wide variety of visitors, from high school and university students, to media, to visiting scholars, as well as graduate students within our laboratory, and interested members of the general public. How have the results been disseminated to communities of interest?The results of this project have been communicated through presentations to audiences throughout the US 1. Innovation in Agricultural Science Lecture: Animal Genome Editing 2017 National Association of State Departments of Agriculture Annual Meeting, New Orleans LA 9/14/2017 2. The Future of Genetic Alteration in Food Animal Production 50thAnnual Conference of the American Association of Bovine Practitioners, Omaha NE 9/15/2017 3. Gene Editing: The Polled Phenotype in Dairy Cattle as a Test case for Social License Breeding for Efficiency 2017 EDGP Symposium, Guelph, Ontario, Canada, 10/16/2017 4. Proposed Regulation of Gene Edited Animals in the U.S. Netherlands Commission on Genetic Modification, Rotterdam The Netherlands 10/20/2017 5. Use of Gene Editing in Cattle Breeding 2017 American Embryo Transfer Association and Canadian Embryo Transfer Association Joint Convention, Orlando FL 10/27/2017 6. Will Genome Editing Be Embraced or Eschewed? North Dakota State University Animal Science Department Graduate Seminar Series, Fargo ND 11/7/2017 7. Regulatory oversight of new breeding innovations in the U.S. TropAgBio2017, QLD Australia 11/19/2017 8. The Use and Impact of Genetic Technologies in the Dairy Industry Professional Dairy Producers of Wisconsin Food & Policy Summit, Madison WI 12/7/2017 9. Evaluation of the Offspring of Genome Edited and Control Bulls Plant and Animal Genome Conference XXVI, San Diego CA 1/16/18 10. Genome Editing Approaches for Livestock - Advancing Animal Health and Welfare Innovation in Agriculture: Women Pioneers at the Frontiers of Science, European Parliament, Belgium 10/15/18 11. Gene Editing in Cattle: Recent developments and prospects Breeding for Efficiency - 2018 Efficient Dairy Genome Project Symposium, Guelph Ontario Canada 12/10/18 12. Food Animal Species: The Importance of Product Risk-based Regulation of Breeding in the Session on Gene Edited Livestock and Regulatory Stalemates. American Association for the Advancement of Science Annual Meeting, Washington DC 2/15/19 13. Genome editing approaches to augmenting livestock breeding programs JEB symposium on Genome editing for comparative physiology Massa Marittima Italy 3/26/19 14. Gene Editing in Food Animals: Prospects and Policy French Academy of Agriculture, Paris France 3/28/19 15. Gene Editing in Cattle: Recent developments and prospects Invited Lecture, INRA, Jouy-en-Josas France 3/29/19 16. Risk Assessment vs Precautionary Principle, Putting Hazard and Perception in their Proper Place for GE Organism Assessments The International Society for Biosafety Research Conference, Tarragona Spain, 4/1/19 17. Genetics, genomics and transgenesis: Impact in animal and food production Great challenges to Science Workshop: How biotechnology can vanish world hunger, Pirassununga SP Brazil 04/12/19 18. Gene Editing in Cattle: Recent developments and prospects Berkeley Innovative Genomics Institute Lecture, Berkeley CA 4/16/19 19.Status of Genome Editing in Food Animals National Coalition Food and Agricultural Research Lunch and Learn Session to both Senate and House Staff, Washington DC 5/20/19 20. Gene editing for Polled Nuffield Council on Bioethics fact-finding meeting, 5/23/19 21. Comparative Evaluation of the Phenotype, Genome and Animal Products Derived from Offspring of a Genome Edited, Hornless Bull and Controls USDA Biotechnology Risk Assessment Project Directors Meeting, Washington DC 6/6/19 22. Update on Gene Editing in Cattle Invited Plenary Speaker, Beef Improvement Federation Annual Research Symposium and Convention, Brookings, SD 6/19/19 23. Enabling Innovation: Genome Editing in plant and animal breeding programs Illinois Farm Bureau Annual Meeting Normal, IL 7/31/2019 24. Detection and characterization of unintended alterations in the offspring of a genome edited, hornless bull Transgenic Animal Research Conference, Tahoe City CA 8/13/19 25. Genetic Improvement in Food Animals: Prospects, Policy, and Public Engagement Department of Plant and Microbial Biology, University of Zurich, Switzerland 9/27/19 26. Genome Editing in Cattle: Recent Developments and Prospects National Beef Cattle Evaluation Consortium Brown Bagger Internet Series 10/23/19 27. How gene editing could be used in dairy breeding programs Dairy Cattle Reproduction Council Annual Meeting, Pittsburg PA 11/14/19 28. Gene Editing in Cattle: Recent developments and regulations Ontario Association of Bovine Practitioners, Guelph ON Canada 11/21/19 29. Regulation of genome editing in animal agriculture: Promises and Policy Teleconference presentation to Genome Editing in Agricultural Research: Applications and Emerging Regulatory Approaches Addis Ababa Ethiopia 12/6/19 30. Gene Editing in Livestock: Prospects and Policy UC Santa Cruz 1/27/20 31. The future of genome editing in food animal species 2020 ASAS-ADSA Meeting, Omaha NE 3/3/20 32. Genome Editing in Livestock UC Berkeley University Extension 3/21/20 33. Genome Engineering for Agricultural Applications Genome Writers Guild 7/23/20 34. Potential of CRISPR in Livestock International Consortium on Applied Bioeconomy Research Annual Program 7/24/20 35. Gene editing in livestock: promise, prospects and policy Arizona State University Animal Science Departmental Seminar 9/21/20 36. Genome Editing Approaches for Livestock --Advancing Animal Health and Welfare Davis Sr High women in Science, Technology, Engineering, and Mathematics 9/29/20 37. Emerging Technologies: Regulatory Oversight of Intentional Genomic Alterations in Animals Food Drug and Law Institute Conference 10/7/20 38. Genome Editing Applications in Animals CRISPR in Agriculture Research, Syntego World CRISPR Day symposium 10/20/20 39. Gene editing in livestock: promise, prospects and policy Iowa State seminar 10/22/20 40. Agricultural animal transgenesis for food applications Transgenic Technology, Israel 10/27/20 41. Using genome editing for livestock health ASAS-Southern Section Genetics and Genomics Webinar Series 11/4/20 42. Genome editing applications in animals Workshop in Genome Editing Technologies, Kenya 11/10/20 43. The importance of innovation to the future of beef production Wagyu International Conference, South Africa 11/11/20 44. Genome editing in livestock National Center for genome editing in agriculture, Israel 1/14/21 45. Genome editing approaches to augment cattle breeding programs British Cattle Breeders Club Conference England 2/1/21 46. How Can We Design a Cow to Better Meet Human Needs? Presentation to two high school classes in MN; 2/3/21, 2/4/21 47. Current Status of Genome editing to Augment Cattle Breeding Programs Board of the American Angus Association, 2/23/21 48. Polled genetics- ready for prime time? Golden State Dairy Management webinar, 3/25/21 49. Gene Editing in Livestock: What is Gene Editing? UC Davis Virtual Picnic Day, 4/17/21 50. Genome Editing in Animals Invited lecture to GMO & Biosafety course, Brac University, Bangladesh 5/5/21 51. Genetic Engineering of Livestock: The Opportunity Cost of Regulatory Delay Invited lecture to Dalhousie University, Faculty of Agriculture, Truro NS Canada 5/6/21 52. Regulation of Gene Editing in Livestock Society for In Vitro Biologys Annual Meeting, SIVB 2021: In Vitro OnLine 6/9/21 53. Gene Editing Today and in the Future Beef Improvement Federation Annual Research Symposium and Convention, Des Moines IA 6/24/21 54. Comparative Evaluation of Human-edible Animal Products Derived from Offspring of Genome Edited and Control Cattle 2021 ASAS-CSAS-SSASAS Annual Meeting and Trade Show, 7/15/21 55. Gene editing in livestock: Science and policy Academy of Veterinary Consultants, Amarillo TX 8/6/21 56. Effective Science Communication to Raise Awareness on Animal Biotechnology ISAAA Impact of Gene Technology in Animal Agriculture and Food Production Workshop 8/31/21 What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
Accomplished under these goals: Objective 1: To obtain offspring from Horned Hereford cows by breeding them to A. a gene edited, polled Holstein bull, B. a Horned Hereford bull, C. a naturally polled Angus bull and D. the horned Holstein sire of the gene edited, polled bull. (2017-2018) - 100% completed? Published. Objective 2: To evaluate the overall health, development and genetic integrity of the offspring obtained in objective 1. (2017-2020) - 100% completed. Published Objective 3: To evaluate the dams that carried the calves sired by the genome edited bull and control bulls for evidence of fetal-maternal microchimerism. (2017-2018) - 100% completed. Published. Objective 4: To evaluate the composition of animal products (milk and meat) derived from the objective 1 offspring in comparison to offspring from control bulls. (2018 - 2020) - 100% completed. Manuscript has been written and submitted to the Journal for Regulatory Science for publication Objective 5: To meet with the U.S. Food and Drug Administration (U.S. FDA) to determine what information should be submitted to Center for Veterinary Medicine (CVM) and the appropriate file type to utilize regarding the experimental animals involved in this experiment. (2019 - 2021) - 100% completed On 8/21/18we requested a Type VII Veterinary Master File (VMF) for the production of intentionally genome altered cattle. A meeting was held in December 2018 with the FDA to establish what information was required to support this file and the appropriate file type to submit that data. At the time we were told to open a VMF to submit a request to CVM to allow entry of the male polled offspring into the human food supply. The requested data regarding the offspring was as follows: 1. Description of animals proposed to enter the food supply: i. Species, class, and number of requested investigational animals (state which animals they would like to enter the food supply: (e.g. 5 male calves sired by IGA bull)). ii. Please clarify if the heifer or sire bull will also be part of the request 2. Breeding strategy used to produce the offspring 3. The purpose of the genetic alteration and the intended function 4. Description of the genetic alteration (location in the genome, (impact on protein expression, if any,) intended sequence, etc.) and details of how the genomic alteration was achieved. 5. Comparison of the genetically altered polled sequence to the naturally occurring polled sequence (sequence alignment) 6. Whole Genome Sequencing (WGS) data for: i. the edited parental animal(s) (including information on which animal(s) the data were collected from and the relation of these animal(s) to the offspring) ii. the unedited cell line (control) iii. at least 2 of the 5 offspring These data should confirm the alteration as well as validate that there are no unintended modifications to the genome that impact animal safety. 7. Health records for the 5 cattle and comparison to non- edited cattle 8. Provide a nutritional compositional analysis of edible muscle tissues of the investigational animals that will enter food supply including key nutrients. This should be compared with equivalent analysis of a conventional counterpart. Provide information on the methodology used and how the samples were obtained to conduct the meat analysis. Also, information regarding any statistical significance of any observed differences related to natural variation. This analysis may focus on muscle, but if available, can also include data on provide liver, kidney and fat. The Codex Guideline (CAC/CL 68-2008) defines key nutrients are those components in a particular food that may have a substantial impact in the overall diet. They may be major constituents (fats, proteins, carbohydrates as nutrients or enzyme inhibitors as anti-nutrients) or minor compounds (minerals, vitamins). ?9. Any concomitant drugs (approved or unapproved) that were used on the animals. 10. Any available information that will help us to conduct the human food safety evaluation (e.g., any feeding studies performed or information from the literature or Recombinetics that you have right-of-reference to that may aid our evaluation). Limit information to those of edited animals at the Celtic allele or relevant (not from conventional breeding). 11. For the bred heifer, if lactating dairy cows are intended to enter the food supply, provide additional information regarding the composition of milk. Data for items 1-7 on the genome edited calves was provided to the FDA (data available BEFORE the animals were killed/had a calf) in December 2018 in a VMF. We subsequently had a conference call with the FDA in May 2019, andwere informed that the only way to get a food use authorization was by opening an Investigational New Animal Drug (INAD), NOT a VMF. The 5 male offspring were subsequently killed, meat was collected to provide the data for point 8 above, nutritional compositional analysis of edible muscle tissues, and then they were incinerated. The female offspring was bred, gave birth, we collected milk from her for the first 4 weeks of lactation (when her calf, who did not inherit the genome edit, died) along with the milk from 4 contemporary control animals, to provide the data for point 11 above. Then the female offspring was killed and meat collected to provide additional nutritional data for point 8. The six cows that gave birth to the genome edited calves were allowed to return to the UC Davis cow herd.
Publications
- Type:
Journal Articles
Status:
Submitted
Year Published:
2021
Citation:
Trott, J.F., Young, A.E., McNabb, B.R., Yang, X., Bishop, T.F., and Van Eenennaam, A.L. Animal health and food safety analyses of six offspring of a genome-edited hornless bull. Journal of Regulatory Science. Submitted 10/13/21
- Type:
Conference Papers and Presentations
Status:
Submitted
Year Published:
2021
Citation:
Trott, J.F., Young, A.E., McNabb, B.R., Yang, X., Bishop, T.F., and Van Eenennaam, A.L. Animal health, food safety, and antibiotic resistance gene expression analyses of six offspring of a genome-edited hornless bull. 16th International Society for Biosafety Research symposium, St. Louis MO, 4/10/21-4/14/21
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2020
Citation:
Young, A.E., Mansour, T.A., McNabb, B.R., Owen, J.R., Trott, J.F., Brown, C.T., and Van Eenennaam, A.L. Detection and characterization of unintended alterations in the offspring of a genome edited, hornless bull. Abstracts from the UC Davis Transgenic Animal Research Conference XII. Transgenic Research 29, 467485 (2020).
https://doi.org/10.1007/s11248-020-00210-1
- Type:
Journal Articles
Status:
Published
Year Published:
2021
Citation:
Van Eenennaam, A.L., Silva, F.D.F., Trott, J.F. and Zilberman, D. Genetic Engineering of Livestock: The Opportunity Cost of Regulatory Delay. Annual Review of Animal Biosciences 2021 9:1, 453-478
https://doi.org/10.1146/annurev-animal-061220-023052
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam, A.L. Application of genome editing in farm animals: cattle. Transgenic Research 28, 93100 (2019)
https://doi.org/10.1007/s11248-019-00141-6
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2021
Citation:
Van Eenennaam, A.L. Genome editing approaches to augment cattle breeding programs. British Cattle Conference, Digest 76: 22-26 (2021)
https://www.cattlebreeders.org.uk/workspace/documents/bcbc2021-digest-01-06-21.pdf
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2021
Citation:
Van Eenennaam, A.L. Gene editing: Today and in the Future. Proceedings of the 53rd Annual Beef Improvement Federation Research Symposium & Convention, pp 33-38 (2021)
https://beefimprovement.org/wp-content/uploads/2021/06/21_BIFProceedings.pdf
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2021
Citation:
Trott, J.F., A. E. Young, B. R. McNabb, X. Yang, T. F. Bishop and A L. Van Eenennaam. Comparative Evaluation Of Human-Edible Animal Products Derived From Offspring Of Genome Edited And Control Cattle. Journal of Animal Science. 99: Issue Supplement_3, 11-12 https://doi.org/10.1093/jas/skab235.020
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2021
Citation:
Van Eenennaam, A. L. 2021. Regulation of Gene Editing in Livestock. The Society for In Vitro Biology virtual meeting. June 5-9, 2021, In Vitro Cellular & Developmental Biology - Animal, 57(SUPPL 1): S6-S6. https://link.springer.com/content/pdf/10.1007/s11626-021-00573-7.pdf
|
Progress 09/01/19 to 08/31/20
Outputs
Target Audience:The target audience includes dairy producers, other researchers, animal scientists, extension specialists, students, veterinarians, industry stakeholders and regulatory representatives. There was tremendous press coverage of this work as detailed in this sampling of the press below. · Why the FDA's Plan to Regulate Gene Editing in Animals Has Some Scientists Worried, Pacific Standard Magazine, 11/1/2018 · https://www.synthego.com/blog/alison-van-eenennamm-podcast Synthego Podcast: Alison Van Eenennaam Edits Cattle Using CRISPR 12/4/2018 · https://www.washingtonpost.com/news/national/wp/2018/12/17/feature/gene-edited-farm-animals-are-coming-will-we-eat-them Washington Post 12/17/2018 · https://www.dairyherd.com/article/gene-editing-finds-its-way-farm Gene Editing finds its Way to the Farm, Dairy Herd Management 12/21/2018 · https://www.flashforwardpod.com/2018/12/18/snip-snip-snip Flash Forward Podcast 12/18/2018 · The Conversation: Gene-edited food regulations: whether it's a plant or animal shouldn't matter, but it does now 2/26/2019 · The Daily Beast: Is a Gene-Edited Animal a Drug? 2/27/2019 · Devex: 3 takeaways for impact in agriculture and development 2/28/2019 · Genetic Literacy Project Podcast: US researchers moving abroad to avoid FDA's CRISPR-edited animal regulations 3/14/2019 · Futurism.com: Scientists Are Fleeing America's Rules About Gene-Editing Animals 3/15/2019 · Wired: A more human livestock industry, brought to you by CRISPR 3/19/2019 · Genetic Literacy Project Viewpoint: FDA plan to regulate gene-edited animals as drugs will thwart US food innovation 4/8/2019 · Pacific Standard: AMERICA'S LEADING ANIMAL GENETICIST WANTS TO TALK TO YOU ABOUT GMOS 4/18/2019 · Genetic Literacy Project Viewpoint: "300 scientists say FDA's plan to regulate CRISPR-edited animals as drugs will effectively shut down innovation" 4/30/2019 · SPLASH Milk Science Update: Genetic Editing Eliminates Dairy Cattle Horns 5/1/2019 · Farmers Weekly: Livestock gene editing: Current rules and potential benefits 6/4/2019 · Bloomberg Business: "Pig Farmers Seek Streamlined Reviews for GMO Pork" 6/25/2019 · DTN Progressive Famer:"Edit FDA regulation for Genes" 6/25/2019 · Feedstuffs Foodlink: "Current U.S. gene editing regulatory framework lags" 6/25/2019 · Farm Journal PORK magazine: "NPPC Campaign Broadens Awareness of Gene Editing's Promise" 6/25/2019 · KTIC Radio: "NPPC LAUNCHES `KEEP AMERICA FIRST IN AGRICULTURE' CAMPAIGN" 6/25/2019 · AgNet West: Industry Concerned with FDA Oversight of Animal Genomics 6/26/2019 · AgWired: "NPPC LAUNCHES `KEEP AMERICA FIRST IN AGRICULTURE' CAMPAIGN" 6/26/2019 · Ohio Ag Net: Edit FDA Regulation for Genes 6/27/2019 Nebraska Corn Board CornsTalk "Food Innovation: GMOs, CRISPR and beyond": Improving Animals through Genetic Innovation" 7/1/2019 · WATTAgNet.com: Gene editing could alleviate ASF's impact on industry 7/3/2019 · High Plains Journal: NPPC stresses importance of keeping up with technology 7/9/2019 · Podcast: Dr. Alison Van Eenennaam - Animal Genetics, Food Marketing, and World Hunger 7/28/2019 · Technology Networks: Grabbing the horns from the bull 8/5/2019 · Wired: We're eating this planet to death 8/8/2019 · AgriNews: U.S. approval process for gene-edited livestock may hamper research 8/26/2019 · AgriNews: Ag research funds in flux with USDA NIFA relocation 8/26/2019 · Technology Networks: Technology Networks Explores the CRISPR Revolution 9/20/2019 · Hoards Dairyman: DCRC Annual Meeting: Genome Editing in Cattle 10/1/2019 · UC Davis News: Genome-Edited Bull Passes on Hornless Trait to Calves 10/7/2019 https://www.ucdavis.edu/news/genome-edited-bull-passes-hornless-trait-calves · BBC News: Genome-Edited Bull Passes Hornless Gene to Calves 10/7/2019 · Grist: Gene editing could help save the planet -- if scientists can avoid the typos 10/7/2019 · Discover Magazine: Scientists Used Gene Editing to Create a Bull Without Horns. It Passed the Trait to its Offspring 10/7/2019 · Sky News: DNA editing sees horned bull father six hornless calves 10/7/2019 · Mirror: Horned bull genetically edited by scientists becomes 'dad' to six hornless calves 10/7/2019 · Eurek Alert!: Genome-edited bull passes on hornless trait to calves10/7/2019 · The Telegraph: Bulls genetically engineered without horns to stop farmers and walkers being gored 10/7/2019 · Daily Democrat: UC Davis breeds bull without horns 10/7/2019 · The Sun: BULL THE OTHER ONE. Mutant bulls without horns created in gene-editing experiment 10/7/2019 · Phys.org: Genome-edited bull passes on hornless trait to calves 10/7/2019 · UC Davis Unfold Podcast: Episode 4 The Future of Food 10/8/2019 · Wired: A Cow, a Controversy, and a Dashed Dream of More Humane Farms 10/8/2019 · Genetic Engineering and Biotechnology News: Hornless Genome-Edited Bull Passes Trait to Offspring 10/8/2019 · AgroPortal: Offspring of gene-edited, hornless dairy bull born healthy, study confirms 10/8/2019 · GenomeWeb: Calves from hornless cattle 10/8/2019 · FirstPost: Gene-edited hornless cattle meat does not get FDA approvcal for human consumption 10/8/2019 · The Mice Times of Asia: Without horns: scientists have deduced new breed of the bulls 10/8/2019 · FarmingUK: Scientists genetically engineer hornless dairy bulls 10/9/2019 · The Standard: Getting gene-edits from stable to table 10/10/2019 · California Dairy Magazine: Genome-Edited Bull Passes on Hornless Trait to Calves 10/10/2019 · California Ag Network: Genome-Edited Bull Passes on Hornless Trait to Calves 10/10/2019 · Associated Press: Gene-edited livestock carry huge promise but major pitfalls 10/12/2019 · The Burn-In: Gene-hacking scientists create bulls with no horns 10/14/2019 · AgNet West: Preventing Horn Growth in Dairy Cows Through Genome Editing 10/16/2019 · Beef Magazine: Accelerated genetic progress 10/16/2019 · ISAAA: Hornless Cattle Now Possible Thanks to Genome-editing 10/16/2019 · The Western Producer: Scientists use gene editing to produce hornless calves 10/17/2019 · Texas Standard: Researchers Use Genome Editing To Breed Hornless Cattle 10/21/2019 · Singularity Hub: CRISPR Just Created a Hornless Bull, and It's a Step Forward for Gene-Edited Food 10/22/2019 · Genetic Literacy Project: Netflix `Unnatural Selection' gene editing miniseries focuses on extreme examples, ignores potential food sustainability impact of CRISPR 10/23/2019 · Progressive Cattle: Gene editing: Does it have a place in the future of beef? 10/24/2019 · That'sFarming: Bull genetically edited to produce hornless calves 10/27/2019 · Capitol Press: Gene-edited food is coming, but will shoppers buy? 11/14/2019 · Technology Networks: Technology Networks Explores the CRISPR Revolution: An Interview With Livestock Geneticist Alison Van Eenennaam 1/6/2020 · Genetic Literacy Project: Geneticist Alison Van Eenennaam explains how the CRISPR gene editing `revolution' can improve our food 1/13/2020 · AgriPulse: FDA: New analysis backs tough regulatory approach to biotech animals 2/7/2020 · ABC National Radio Background Briefing: Mutants or miracles? Australia's GM cows 3/15/2020 · ABC Television: Landline: GM cows: Genetically modifying dairy cattle 3/15/2020 · ABC National Radio AM: "No big deal": modified cattle in Victoria carried genetic contamination 3/14/2020 Changes/Problems:We are delayed by a year because it took longer than expected for the heifer to become pregnant and maintain her pregnancy, and we have also been slowed down due to COVID-19 shutting down non-essential research at the University of California Davis. What opportunities for training and professional development has the project provided?The animals have served as educational and training examples for a wide variety of visitors, from high school and university students, to media, to visiting scholars, as well as graduate students within our laboratory, and interested members of the general public. How have the results been disseminated to communities of interest?"Genome Editing Approaches for Livestock - Advancing Animal Health and Welfare" Innovation in Agriculture: Women Pioneers at the Frontiers of Science, European Parliament, Brussels, Belgium 10/15/2018 "Gene Editing in Agrifood: Its Promises and Prospects" Round table with Portuguese Government Officials, Lisbon, Portugal 10/17/2018 "Gene Editing in Agrifood: Its Promises and Prospects" Round table with Spanish Government Officials, Madrid, Spain 10/18/2018 "The promise of combining advanced reproductive technologies and genomics in cattle breeding programs", University of Tennessee, Knoxville, TN 10/29/2018 "Gene Editing and the Future of Bovine Genetics" 15th International Symposium on Milk Genomics & Human Health, Sacramento, CA 11/13/2018 "Gene Editing and Food Evolution, American Agri-women conference, Springfield, Ilinois 11/16/2018 "Enabling Innovation in Agricultural Breeding Programs: Promises and Prospects", Presentation to the Ugandan Ministry of Science, Technology and Innovation, Kampala, Uganda 11/30/2018 "Gene Editing in Cattle: Recent developments and prospects", Breeding for Efficiency - 2018 Efficient Dairy Genome Project Symposium, Guelph, Ontario, Canada 12/10/2018 "Food Animal Species: The Importance of Product Risk-based Regulation of Breeding" in the Session on Gene Edited Livestock and Regulatory Stalemates. American Association for the Advancement of Science (AAAS) Annual Meeting, Washington DC, 2/15/2019 "The Role of Genetic Improvement on the Sustainability of Animal Agriculture" 2019 Midwest Veterinary Conference, Columbus, OH 2/21/2019 "Understanding Genomics, Genetic Engineering, and Gene Editing" 2019 Midwest Veterinary Conference, Columbus, OH 2/22/2019 "Gene Editing: Designing the Farm Animals and Fish of Tomorrow" Panel, Animal AgTech Innovation Summit, San Francisco, CA 3/18/2019 "A Deep Dive into Next Generation Breeding Technologies" Panel, World Agri-Tech Innovation Summit, San Francisco, CA 3/19/2019 "Genome editing approaches to augmenting livestock breeding programs", JEB symposium on `Genome editing for comparative physiology' Massa Marittima, Italy 3/26/2019 "Gene Editing in Food Animals: Prospects and Policy" French Academy of Agriculture, Paris, France 3/28/2019 "Gene Editing in Cattle: Recent developments and prospects" Invited Lecture, INRA, Jouy-en-Josas, France 3/29/2019 "Risk Assessment vs Precautionary Principle, Putting Hazard and Perception in their Proper Place for GE Organism Assessments" The International Society for Biosafety Research Conference, Tarragona Spain, 4/1/2019 "Enabling Innovation in Agricultural Breeding Programs: Promises and Prospects" The International Society for Biosafety Research Conference, Tarragona Spain, 4/4/2019 "Genetics, genomics and transgenesis: Impact in animal and food production" How biotechnology can vanish world hunger Workshop: Great challenges to Science Pirassununga, SP, Brazil, 04/12/2019 "Gene Editing in Cattle: Recent developments and prospects", Berkeley Innovative Genomics Institute Lecture, Berkeley, CA 4/16/2019 "Genetic Improvement in Food Animals: Prospects, Policy, and Public Engagement ", University and Industry Consortium, Madison, WI 4/17/2019 "Does the Animal Drug Rubric Make Sense?", University and Industry Consortium, Madison, WI 4/18/2019 "Enabling Innovation in Agricultural Breeding Programs: Promises and Prospects", UC Davis College of Agriculture and Environmental Sciences (CAES) Dean's Advisory Council Meeting, Davis, CA 4/25/2019 "Regulation of genome editing in animal agriculture: Promises and Policy", PBS (Program for Biosafety Systems), Intenet video conference to Kenya, 4/25/2019 "Enabling Innovation in Agricultural Breeding Programs: Promises and Policy", One Health Symposium, University of Delaware, DE 04/30/2019 "Status of Genome Editing in Food Animals", National Coalition Food and Agricultural Research (NCFAR) Lunch and Learn Session to both Senate and House Staff, Washington DC, 5/20/2019 "Gene editing for Polled", Nuffield Council on Bioethics fact-finding meeting, Internet conference, 5/23/2019 "CRISPR and Genetics and Welfare", Dairy Cattle Welfare Symposium, Orlando, FL 5/29/2019 "Comparative Evaluation of the Phenotype, Genome and Animal Products Derived from Offspring of a Genome Edited, Hornless Bull and Controls", USDA Biotechnology Risk Assessment Project Directors' Meeting, Washington DC, 6/6/2019 "Genome Editing in Agriculture: Prospects and Potential Pitfalls" Ospraie Management Biennial Symposium, Invited Keynote speaker, Deer Valley, UT 6/12/2019 "Update on Gene Editing in Cattle" Invited Plenary Speaker, Beef Improvement Federation Annual Research Symposium and Convention, Brookings, SD 6/19/2019 "Overview of Gene Editing Technology", National Pork Producers Council Gene Editing Media Teleconference, Washington DC, 6/25/2019 "Importance of Innovation to Agricultural Sustainability" Invited Keynote Speaker, University of Guelph Agri-Food Excellence Symposium Guelph, Canada 6/25/2019 "The importance of genetic improvement to the sustainability of animal agriculture", Invited Awardee Presentation, Rockefeller Prentice Award in Animal Breeding and Genetics, ASAS Annual meeting, Austin, TX 7/11/2019 "Enabling Innovation: Genome Editing in plant and animal breeding programs", Illinois Farm Bureau Annual Meeting Normal, IL 7/31/2019 "Detection and characterization of unintended alterations in the offspring of a genome edited, hornless bull", Transgenic Animal Research Conference, Tahoe City, CA 8/13/2019 "Use of Biotechnology and Genomics in Sustainable Livestock Systems", Global Agenda for Sustainable Livestock (GASL) Multi Stakeholder Partnership (MSP) meeting , Manhattan, KS 9/9/2019 "Genetic Improvement in Food Animals: Prospects, Policy, and Public Engagement", Cornell Alliance for Science 2019 Global Leadership Fellows Training Program, Ithaca, NY 9/17/2019 "Genetic Improvement in Food Animals: Prospects, Policy, and Public Engagement", Department of Plant and Microbial Biology, University of Zurich, Switzerland 9/27/2019 "Genome Editing in Cattle: Recent Developments and Prospects", National Beef Cattle Evaluation Consortium Brown Bagger Internet Series, Teleconference, 10/23/2019 The importance of Innovation to the Sustainability of Animal Agriculture", BBSRC Cross-Institute Workshop: The future role of livestock in food production, Roslin Institute, Edinburgh, Scotland 11/11/2019 "How gene editing could be used in dairy breeding programs", Dairy Cattle Reproduction Council (DCRC) Annual Meeting, Pittsburg, PA 11/14/2019 "Gene Editing in Cattle: Recent developments and regulations" Ontario Association of Bovine Practitioners (OABP), Guelph, ON, Canada, 11/21/2019 "Regulation of genome editing in animal agriculture: Promises and Policy", Teleconference presentation to "Genome Editing in Agricultural Research: Applications and Emerging Regulatory Approaches", Addis Ababa, Ethiopia, 12/6/2019 "Development of advanced biotechnologies to improve the efficiency of animal agriculture", Presentation to Advanced Research Projects Agency-Energy (ARPA-E), Davis, CA 12/12/2019 "How Regulatory Factors Influence the Application of Genomics in Animals", Plant and Animal Genome Conference , San Diego, CA 1/13/2020 "Embryo gene editing: techniques, uses and future perspectives", Narrowing the gaps between embryo gene editing and ethics" International Embryo Technology Society (IETS), New York, NY 1/18/2020 "Gene Editing in Livestock: Prospects and Policy", UC Santa Cruz, 1/27/2020 "The future of genome editing in food animal species", 2020 ASAS-ADSA Meeting, Omaha, NE 3/3/2020 "Genome Editing in Livestock", UC Berkeley University Extension, 3/21/2020 "Genome Engineering for Agricultural Applications" Genome Writer's Guild, 7/23/2020 What do you plan to do during the next reporting period to accomplish the goals? During the next reporting period, we plan to collect milk and meat from the female offspring of the genome-edited bull and analyze all the meat and milk samples for nutritional content. To this end we have already collected milk samples from other beef cattle at UC Davis, including purebred Herefords (n=2), a Hereford/Angus heifer and the control heifer with a 25% coefficient of relationship with the genome-edited heifer. We have milk samples starting at 1 week after parturition collected weekly out to 7 weeks post-parturition for the four non genome-edited beef cows. We will collect milk from our one female offspring of the genome-edited bull starting at 1 week out to 7 weeks post-parturition. These milk samples will be analyzed for milk component testing (fat, protein, lactose, solids, and casein), in addition to specific analyses for Ca, P, Mg, K, Na, S and Cl. This cow will be kept until the calf is 6 months old and weaned, then she and the calf will be euthanized, samples of chuck and sirloin collected from the cow for the same meat analyses performed on the 5 male offspring, and then she and the calf will be incinerated as unapproved new animal drugs September, 2020 - Final milk sample will be taken December, 2020 - Milk analyses data received and statistical analyses completed. Manuscript writing begins. February, 2021 - Grandchild of genome-edited bull weaned. Dam will be euthanized, chuck arm and sirloin cap collected and analyzed by Eurofins. Animal will be incinerated August 2021 - Complete writing the second manuscript about the phenotypes of and animal products derived from genome-edited offspring.
Impacts
What was accomplished under these goals?
Objective 1: To obtain offspring from Horned Hereford cows by breeding them to A. a gene edited, polled Holstein bull, B. a Horned Hereford bull, C. a naturally polled Angus bull and D. the horned Holstein sire of the gene edited, polled bull. (2017-2018) - 100% completed Published. Objective 2: To evaluate the overall health, development and genetic integrity of the offspring obtained in objective 1. (2017-2020) - 90% completed All of this data has been collected and we are in the process of writing up the manuscript. Objective 3: To evaluate the dams that carried the calves sired by the genome edited bull and control bulls for evidence of fetal-maternal microchimerism. (2017-2018) - 100% completed Published. Objective 4: To evaluate the composition of animal products (milk and meat) derived from the objective 1 offspring in comparison to offspring from control bulls. (2018 - 2020) - 60% completed The five male offspring of the genome-edited bull were euthanized and incinerated in 2019. We collected a sample of chuck arm and sirloin cap from all five bulls. We also collected chuck arm and sirloin cap samples from two bulls with a 25% coefficient of relationship with the genome-edited offspring (controls). These two bulls were slaughtered and entered the food chain as they were control animals and did not contain any "intentional genomic alterations". We used Eurofins Microbiology Laboratories to get proximate analyses (fat, protein, carbohydrate, water, calories and ash), iron and Vitamin B12 content for the chuck arm (n=7), sirloin cap (n=7) and tritip (n=1 genome edited bull). We also analyzed a subset of meat (n=3 offspring of the genome-edited bull, n=1 control) more extensively for important nutritional parameters specific to meat, including eighteen of the twenty amino acids, riboflavin, niacin, Vitamin B6, phosphorus and zinc. These were analyzed for both chuck and sirloin samples from the 4 bulls. The single female offspring of the genome-edited bull was bred to a horned Hereford bull and gave birth in August 2020. Objective 5: To meet with the U.S. Food and Drug Administration (U.S. FDA) to determine what information should be submitted to Center for Veterinary Medicine (CVM) and the appropriate file type to utilize regarding the experimental animals involved in this experiment. (2019 - 2020) - 50% completed On August 21, 2018 we requested a Type VII Veterinary Master File (VMF) for the production of intentionally genome altered cattle. A meeting was held in December 2018 with the FDA to establish what information was required to support this file and the appropriate file type to submit that data. At the time we were told to open a VMF to submit a request to CVM to allow entry of the male polled offspring into the human food supply. The requested data regarding the offspring was as follows: 1. Description of animals proposed to enter the food supply: i. Species, class, and number of requested investigational animals (state which animals they would like to enter the food supply: (e.g. 5 male calves sired by IGA bull)). ii. Please clarify if the heifer or sire bull will also be part of the request 2. Breeding strategy used to produce the offspring 3. The purpose of the genetic alteration and the intended function 4. Description of the genetic alteration (location in the genome, (impact on protein expression, if any,) intended sequence, etc.) and details of how the genomic alteration was achieved. 5. Comparison of the genetically altered polled sequence to the naturally occurring polled sequence (sequence alignment) 6. Whole Genome Sequencing (WGS) data for: i. the edited parental animal(s) (including information on which animal(s) the data were collected from and the relation of these animal(s) to the offspring) i. the unedited cell line (control) ii. at least 2 of the 5 offspring These data should confirm the alteration as well as validate that there are no unintended modifications to the genome that impact animal safety. 7. Health records for the 5 cattle and comparison to non- edited cattle 8. Provide a nutritional compositional analysis of edible muscle tissues of the investigational animals that will enter food supply including key nutrients. This should be compared with equivalent analysis of a conventional counterpart. Provide information on the methodology used and how the samples were obtained to conduct the meat analysis. Also, information regarding any statistical significance of any observed differences related to natural variation. This analysis may focus on muscle, but if available, can also include data on provide liver, kidney and fat. The Codex Guideline (CAC/CL 68-2008) defines key nutrients are those components in a particular food that may have a substantial impact in the overall diet. They may be major constituents (fats, proteins, carbohydrates as nutrients or enzyme inhibitors as anti-nutrients) or minor compounds (minerals, vitamins). 9. Any concomitant drugs (approved or unapproved) that were used on the animals. 10. Any available information that will help us to conduct the human food safety evaluation (e.g., any feeding studies performed or information from the literature or Recombinetics that you have right-of-reference to that may aid our evaluation). Limit information to those of edited animals at the Celtic allele or relevant (not from conventional breeding). 11. For the bred heifer, if lactating dairy cows are intended to enter the food supply, provide additional information regarding the composition of milk. Data for items 1-7 on the genome edited calves was provided to the FDA (data available BEFORE the animals were killed/had a calf) in December 2018 in a VMF. We subsequently had a conference call with the FDA in May 2019, and we were informed that the only way to get a food use authorization was by opening an Investigational New Animal Drug (INAD), NOT a VMF. The 5 male offspring were subsequently killed, meat was collected to provide the data for point 8 above, nutritional compositional analysis of edible muscle tissues, and then they were incinerated. The female offspring was bred to provide the data for point 11 above, information regarding the composition of milk, and then both she and her calf will also be incinerated. The six cows that gave birth to the genome edited calves were allowed to return to the UC Davis cow herd.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Young, A.E., T.A. Mansour, B.R. McNabb, J.R. Owen, J.F.Trott, C.T. Brown, and A.L. Van Eenennaam, 2020. Comparative evaluation of the phenotype and genome from offspring of a genome edited, hornless bull and controls. Nature Biotechnology 38. 225-232.
DOI: https://doi.org/10.1038/s41587-019-0266-0
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Bishop, T.F., and Van Eenennaam, A.L. 2020 Genome editing approaches to augment livestock breeding programs. J Exp Biol. 2020 Feb 7;223(Pt Suppl 1). pii: jeb207159.
- Type:
Book Chapters
Status:
Published
Year Published:
2018
Citation:
Van Eenennaam, A.L. and A. E. Young. 2018. �Public Perception of Animal Biotechnology, H. Niemann & C. Wrenzycki (ed)�Animal Biotechnology 2. Emerging Breeding Technologies, 275-303
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Van Eenennaam, A.L., Young, A. E. 2018. Public Perception of Animal Biotechnology. Keystone Symposium: Leveraging Genomic Diversity to Promote Animal and Human Health, November 25-29, 2018, Kampala, Uganda
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam, A.L. 2019. Food Animal Species: The Importance of Product Risk-based Regulation of Breeding, American Association Advacement of Science (AAAS) Annual Meeting, February 14-17, 2019, Washington DC
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam, A.L. 2019. The role of genetic improvement on the sustainability of animal agriculture. Midwest Veterinary Conference, February 21-22, 2019, Columbus, OH
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam, A.L. 2019. Understanding genomics, genetic engineering, and gene editing. Midwest Veterinary Conference, February 21-22, 2019, Columbus, OH
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam, A.L. 2019. Genome editing approaches to augmenting livestock breeding programs. JEB 2019 Symposium on `Genome editing for comparative physiology', March 23-26, 2019. Tenuta il Cicalino, Italy
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2019
Citation:
Van Eenennaam, A. L. Enabling Innovation in Agricultural Breeding Programs: Promises and Prospects. The International Society for Biosafety Research Conference, Tarragona Spain, April 1-4, 2019
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
an Eenennaam A. L. Genetics, genomics and transgenesis: Impact in Animal and food production. How biotechnology can vanish world hunger Workshop: Great challenges to science. Campus da USP Fernando Costa , Pirassununga, SP, Brazil, 04/11-13/2019
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam, A. L. 2019. Genome editing in cattle: Recent developments and prospects. Proceedings of the 2019 Dairy Cattle Reproduction Council Conference. Pittsburgh, PA pp 86-96.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2020
Citation:
Van Eenennaam, A.L. 2020. How Regulatory Factors Influence the Application of Genomics in Animals. Plant and Animal Genome XXVII Conference Abstract #W684
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Progress 09/01/18 to 08/31/19
Outputs
Target Audience: The target audience includes dairy producers, other researchers, animal scientists, extension specialists, students, veterinarians, industry stakeholders and regulatory representatives. There was tremendous press coverage of this work as detailed in this sampling of the press below. · Why the FDA's Plan to Regulate Gene Editing in Animals Has Some Scientists Worried, Pacific Standard Magazine, 11/1/2018 · https://www.synthego.com/blog/alison-van-eenennamm-podcast Synthego Podcast: Alison Van Eenennaam Edits Cattle Using CRISPR 12/4/2018 · https://www.washingtonpost.com/news/national/wp/2018/12/17/feature/gene-edited-farm-animals-are-coming-will-we-eat-them Washington Post 12/17/2018 · https://www.dairyherd.com/article/gene-editing-finds-its-way-farm Gene Editing finds its Way to the Farm, Dairy Herd Management 12/21/2018 · https://www.flashforwardpod.com/2018/12/18/snip-snip-snip Flash Forward Podcast 12/18/2018 · The Conversation: Gene-edited food regulations: whether it's a plant or animal shouldn't matter, but it does now 2/26/2019 · The Daily Beast: Is a Gene-Edited Animal a Drug? 2/27/2019 · Devex: 3 takeaways for impact in agriculture and development 2/28/2019 · Genetic Literacy Project Podcast: US researchers moving abroad to avoid FDA's CRISPR-edited animal regulations 3/14/2019 · Futurism.com: Scientists Are Fleeing America's Rules About Gene-Editing Animals 3/15/2019 · Wired: A more human livestock industry, brought to you by CRISPR 3/19/2019 · Genetic Literacy Project Viewpoint: FDA plan to regulate gene-edited animals as drugs will thwart US food innovation 4/8/2019 · Pacific Standard: AMERICA'S LEADING ANIMAL GENETICIST WANTS TO TALK TO YOU ABOUT GMOS 4/18/2019 · Genetic Literacy Project Viewpoint: "300 scientists say FDA's plan to regulate CRISPR-edited animals as drugs will effectively shut down innovation" 4/30/2019 · SPLASH Milk Science Update: Genetic Editing Eliminates Dairy Cattle Horns 5/1/2019 · Farmers Weekly: Livestock gene editing: Current rules and potential benefits 6/4/2019 · Bloomberg Business: "Pig Farmers Seek Streamlined Reviews for GMO Pork" 6/25/2019 · DTN Progressive Famer:"Edit FDA regulation for Genes" 6/25/2019 · Feedstuffs Foodlink: "Current U.S. gene editing regulatory framework lags" 6/25/2019 · Farm Journal PORK magazine: "NPPC Campaign Broadens Awareness of Gene Editing's Promise" 6/25/2019 · KTIC Radio: "NPPC LAUNCHES `KEEP AMERICA FIRST IN AGRICULTURE' CAMPAIGN" 6/25/2019 · AgNet West: Industry Concerned with FDA Oversight of Animal Genomics 6/26/2019 · AgWired: "NPPC LAUNCHES `KEEP AMERICA FIRST IN AGRICULTURE' CAMPAIGN" 6/26/2019 · Ohio Ag Net: Edit FDA Regulation for Genes 6/27/2019 Nebraska Corn Board CornsTalk "Food Innovation: GMOs, CRISPR and beyond": Improving Animals through Genetic Innovation" 7/1/2019 · WATTAgNet.com: Gene editing could alleviate ASF's impact on industry 7/3/2019 · High Plains Journal: NPPC stresses importance of keeping up with technology 7/9/2019 · Podcast: Dr. Alison Van Eenennaam - Animal Genetics, Food Marketing, and World Hunger 7/28/2019 · Technology Networks: Grabbing the horns from the bull 8/5/2019 · Wired: We're eating this planet to death 8/8/2019 · AgriNews: U.S. approval process for gene-edited livestock may hamper research 8/26/2019 · AgriNews: Ag research funds in flux with USDA NIFA relocation 8/26/2019 · Technology Networks: Technology Networks Explores the CRISPR Revolution 9/20/2019 · Hoards Dairyman: DCRC Annual Meeting: Genome Editing in Cattle 10/1/2019 · UC Davis News: Genome-Edited Bull Passes on Hornless Trait to Calves 10/7/2019 https://www.ucdavis.edu/news/genome-edited-bull-passes-hornless-trait-calves · BBC News: Genome-Edited Bull Passes Hornless Gene to Calves 10/7/2019 · Grist: Gene editing could help save the planet -- if scientists can avoid the typos 10/7/2019 · Discover Magazine: Scientists Used Gene Editing to Create a Bull Without Horns. It Passed the Trait to its Offspring 10/7/2019 · Sky News: DNA editing sees horned bull father six hornless calves 10/7/2019 · Mirror: Horned bull genetically edited by scientists becomes 'dad' to six hornless calves 10/7/2019 · Eurek Alert!: Genome-edited bull passes on hornless trait to calves10/7/2019 · The Telegraph: Bulls genetically engineered without horns to stop farmers and walkers being gored 10/7/2019 · Daily Democrat: UC Davis breeds bull without horns 10/7/2019 · The Sun: BULL THE OTHER ONE. Mutant bulls without horns created in gene-editing experiment 10/7/2019 · Phys.org: Genome-edited bull passes on hornless trait to calves 10/7/2019 · UC Davis Unfold Podcast: Episode 4 The Future of Food 10/8/2019 · Wired: A Cow, a Controversy, and a Dashed Dream of More Humane Farms 10/8/2019 · Genetic Engineering and Biotechnology News: Hornless Genome-Edited Bull Passes Trait to Offspring 10/8/2019 · AgroPortal: Offspring of gene-edited, hornless dairy bull born healthy, study confirms 10/8/2019 · GenomeWeb: Calves from hornless cattle 10/8/2019 · FirstPost: Gene-edited hornless cattle meat does not get FDA approvcal for human consumption 10/8/2019 · The Mice Times of Asia: Without horns: scientists have deduced new breed of the bulls 10/8/2019 · FarmingUK: Scientists genetically engineer hornless dairy bulls 10/9/2019 · The Standard: Getting gene-edits from stable to table 10/10/2019 · California Dairy Magazine: Genome-Edited Bull Passes on Hornless Trait to Calves 10/10/2019 · California Ag Network: Genome-Edited Bull Passes on Hornless Trait to Calves 10/10/2019 · Associated Press: Gene-edited livestock carry huge promise but major pitfalls 10/12/2019 · The Burn-In: Gene-hacking scientists create bulls with no horns 10/14/2019 · AgNet West: Preventing Horn Growth in Dairy Cows Through Genome Editing 10/16/2019 · Beef Magazine: Accelerated genetic progress 10/16/2019 · ISAAA: Hornless Cattle Now Possible Thanks to Genome-editing 10/16/2019 · The Western Producer: Scientists use gene editing to produce hornless calves 10/17/2019 · Texas Standard: Researchers Use Genome Editing To Breed Hornless Cattle 10/21/2019 · Singularity Hub: CRISPR Just Created a Hornless Bull, and It's a Step Forward for Gene-Edited Food 10/22/2019 · Genetic Literacy Project: Netflix `Unnatural Selection' gene editing miniseries focuses on extreme examples, ignores potential food sustainability impact of CRISPR 10/23/2019 · Progressive Cattle: Gene editing: Does it have a place in the future of beef? 10/24/2019 · That'sFarming: Bull genetically edited to produce hornless calves 10/27/2019 · Capitol Press: Gene-edited food is coming, but will shoppers buy? 11/14/2019 · Technology Networks: Technology Networks Explores the CRISPR Revolution: An Interview With Livestock Geneticist Alison Van Eenennaam 1/6/2020 · Genetic Literacy Project: Geneticist Alison Van Eenennaam explains how the CRISPR gene editing `revolution' can improve our food 1/13/2020 · AgriPulse: FDA: New analysis backs tough regulatory approach to biotech animals 2/7/2020 · ABC National Radio Background Briefing: Mutants or miracles? Australia's GM cows 3/15/2020 · ABC Television: Landline: GM cows: Genetically modifying dairy cattle 3/15/2020 · ABC National Radio AM: "No big deal": modified cattle in Victoria carried genetic contamination 3/14/2020 Changes/Problems:We are delayed by a year because it took longer than expected for the heifer to become pregnant and maintain her pregnancy, and we have also been slowed down due to COVID-19 shutting down non-essential research at the University of California Davis. What opportunities for training and professional development has the project provided?The animals have served as educational and training examples for a wide variety of visitors, from high school and university students, to media, to visiting scholars, as well as graduate students within our laboratory, and interested members of the general public. How have the results been disseminated to communities of interest?"Genome Editing Approaches for Livestock - Advancing Animal Health and Welfare" Innovation in Agriculture: Women Pioneers at the Frontiers of Science, European Parliament, Brussels, Belgium 10/15/2018 "Gene Editing in Agrifood: Its Promises and Prospects" Round table with Portuguese Government Officials, Lisbon, Portugal 10/17/2018 "Gene Editing in Agrifood: Its Promises and Prospects" Round table with Spanish Government Officials, Madrid, Spain 10/18/2018 "The promise of combining advanced reproductive technologies and genomics in cattle breeding programs", University of Tennessee, Knoxville, TN 10/29/2018 "Gene Editing and the Future of Bovine Genetics" 15th International Symposium on Milk Genomics & Human Health, Sacramento, CA 11/13/2018 "Gene Editing and Food Evolution, American Agri-women conference, Springfield, Ilinois 11/16/2018 "Enabling Innovation in Agricultural Breeding Programs: Promises and Prospects", Presentation to the Ugandan Ministry of Science, Technology and Innovation, Kampala, Uganda 11/30/2018 "Gene Editing in Cattle: Recent developments and prospects", Breeding for Efficiency - 2018 Efficient Dairy Genome Project Symposium, Guelph, Ontario, Canada 12/10/2018 "Food Animal Species: The Importance of Product Risk-based Regulation of Breeding" in the Session on Gene Edited Livestock and Regulatory Stalemates. American Association for the Advancement of Science (AAAS) Annual Meeting, Washington DC, 2/15/2019 "The Role of Genetic Improvement on the Sustainability of Animal Agriculture" 2019 Midwest Veterinary Conference, Columbus, OH 2/21/2019 Understanding Genomics, Genetic Engineering, and Gene Editing" 2019 Midwest Veterinary Conference, Columbus, OH 2/22/2019 "Gene Editing: Designing the Farm Animals and Fish of Tomorrow" Panel, Animal AgTech Innovation Summit, San Francisco, CA 3/18/2019 "A Deep Dive into Next Generation Breeding Technologies" Panel, World Agri-Tech Innovation Summit, San Francisco, CA 3/19/2019 "Genome editing approaches to augmenting livestock breeding programs", JEB symposium on `Genome editing for comparative physiology' Massa Marittima, Italy 3/26/2019 "Gene Editing in Food Animals: Prospects and Policy" French Academy of Agriculture, Paris, France 3/28/2019 "Gene Editing in Cattle: Recent developments and prospects" Invited Lecture, INRA, Jouy-en-Josas, France 3/29/2019 "Risk Assessment vs Precautionary Principle, Putting Hazard and Perception in their Proper Place for GE Organism Assessments" The International Society for Biosafety Research Conference, Tarragona Spain, 4/1/2019 "Enabling Innovation in Agricultural Breeding Programs: Promises and Prospects" The International Society for Biosafety Research Conference, Tarragona Spain, 4/4/2019 "Genetics, genomics and transgenesis: Impact in animal and food production" How biotechnology can vanish world hunger Workshop: Great challenges to Science Pirassununga, SP, Brazil, 04/12/2019 "Gene Editing in Cattle: Recent developments and prospects", Berkeley Innovative Genomics Institute Lecture, Berkeley, CA 4/16/2019 "Genetic Improvement in Food Animals: Prospects, Policy, and Public Engagement ", University and Industry Consortium, Madison, WI 4/17/2019 "Does the Animal Drug Rubric Make Sense?", University and Industry Consortium, Madison, WI 4/18/2019 "Enabling Innovation in Agricultural Breeding Programs: Promises and Prospects", UC Davis College of Agriculture and Environmental Sciences (CAES) Dean's Advisory Council Meeting, Davis, CA 4/25/2019 "Regulation of genome editing in animal agriculture: Promises and Policy", PBS (Program for Biosafety Systems), Internet video conference to Kenya, 4/25/2019 "Enabling Innovation in Agricultural Breeding Programs: Promises and Policy", One Health Symposium, University of Delaware, DE 04/30/2019 "Status of Genome Editing in Food Animals", National Coalition Food and Agricultural Research (NCFAR) Lunch and Learn Session to both Senate and House Staff, Washington DC, 5/20/2019 "Gene editing for Polled", Nuffield Council on Bioethics fact-finding meeting, Internet conference, 5/23/2019 "CRISPR and Genetics and Welfare", Dairy Cattle Welfare Symposium, Orlando, FL 5/29/2019 "Comparative Evaluation of the Phenotype, Genome and Animal Products Derived from Offspring of a Genome Edited, Hornless Bull and Controls", USDA Biotechnology Risk Assessment Project Directors' Meeting, Washington DC, 6/6/2019 "Genome Editing in Agriculture: Prospects and Potential Pitfalls" Ospraie Management Biennial Symposium, Invited Keynote speaker, Deer Valley, UT 6/12/2019 "Update on Gene Editing in Cattle" Invited Plenary Speaker, Beef Improvement Federation Annual Research Symposium and Convention, Brookings, SD 6/19/2019 "Overview of Gene Editing Technology", National Pork Producers Council Gene Editing Media Teleconference, Washington DC, 6/25/2019 "Importance of Innovation to Agricultural Sustainability" Invited Keynote Speaker, University of Guelph Agri-Food Excellence Symposium Guelph, Canada 6/25/2019 "The importance of genetic improvement to the sustainability of animal agriculture", Invited Awardee Presentation, Rockefeller Prentice Award in Animal Breeding and Genetics, ASAS Annual meeting, Austin, TX 7/11/2019 "Enabling Innovation: Genome Editing in plant and animal breeding programs", Illinois Farm Bureau Annual Meeting Normal, IL 7/31/2019 "Detection and characterization of unintended alterations in the offspring of a genome edited, hornless bull", Transgenic Animal Research Conference, Tahoe City, CA 8/13/2019 "Use of Biotechnology and Genomics in Sustainable Livestock Systems", Global Agenda for Sustainable Livestock (GASL) Multi Stakeholder Partnership (MSP) meeting , Manhattan, KS 9/9/2019 "Genetic Improvement in Food Animals: Prospects, Policy, and Public Engagement", Cornell Alliance for Science 2019 Global Leadership Fellows Training Program, Ithaca, NY 9/17/2019 "Genetic Improvement in Food Animals: Prospects, Policy, and Public Engagement", Department of Plant and Microbial Biology, University of Zurich, Switzerland 9/27/2019 "Genome Editing in Cattle: Recent Developments and Prospects", National Beef Cattle Evaluation Consortium Brown Bagger Internet Series, Teleconference, 10/23/2019 The importance of Innovation to the Sustainability of Animal Agriculture", BBSRC Cross-Institute Workshop: The future role of livestock in food production, Roslin Institute, Edinburgh, Scotland 11/11/2019 "How gene editing could be used in dairy breeding programs", Dairy Cattle Reproduction Council (DCRC) Annual Meeting, Pittsburg, PA 11/14/2019 "Gene Editing in Cattle: Recent developments and regulations" Ontario Association of Bovine Practitioners (OABP), Guelph, ON, Canada, 11/21/2019 "Regulation of genome editing in animal agriculture: Promises and Policy", Teleconference presentation to "Genome Editing in Agricultural Research: Applications and Emerging Regulatory Approaches", Addis Ababa, Ethiopia, 12/6/2019 "Development of advanced biotechnologies to improve the efficiency of animal agriculture", Presentation to Advanced Research Projects Agency-Energy (ARPA-E), Davis, CA 12/12/2019 "How Regulatory Factors Influence the Application of Genomics in Animals", Plant and Animal Genome Conference , San Diego, CA "Embryo gene editing: techniques, uses and future perspectives", Narrowing the gaps between embryo gene editing and ethics" International Embryo Technology Society (IETS), New York, NY 1/18/2020 "Gene Editing in Livestock: Prospects and Policy", UC Santa Cruz, 1/27/2020 "The future of genome editing in food animal species", 2020 ASAS-ADSA Meeting, Omaha, NE 3/3/2020 "Genome Editing in Livestock", UC Berkeley University Extension, 3/21/2020 "Genome Engineering for Agricultural Applications" Genome Writer's Guild, 7/23/2020 What do you plan to do during the next reporting period to accomplish the goals?During the next reporting period, we plan to collect milk and meat from the female offspring of the genome-edited bull and analyze all the meat and milk samples for nutritional content.To this end we have already collected milk samples from other beef cattle at UC Davis, including purebred Herefords (n=2), a Hereford/Angus heifer and the control heifer with a 25% coefficient of relationship with the genome-edited heifer. We have milk samples starting at 1 week after parturition collected weekly out to 7 weeks post-parturition for the four non genome-edited beef cows. We will collect milk from our one female offspring of the genome-edited bull starting at 1 week out to 7 weeks post-parturition.These milk samples will be analyzed for milk component testing (fat, protein, lactose, solids, and casein), in addition to specific analyses for Ca, P, Mg, K, Na, S and Cl. This cow will be kept until the calf is 6 months old and weaned, then she and the calf will be euthanized, samples of chuck and sirloin collected from the cow for the same meat analyses performed on the 5 male offspring, and then she and the calf will be incinerated as unapproved new animal drugs September, 2020- Final milk sample will be taken December, 2020- Milk analyses data received and statistical analyses completed. Manuscript writing begins. February, 2021- Grandchild of genome-edited bull weaned. Dam will be euthanized, chuck arm and sirloin cap collected and analyzed by Eurofins. Animal will be incinerated August 2021- Complete writing the second manuscript about the phenotypes of and animal products derived from genome-edited offspring.
Impacts
What was accomplished under these goals?
Obj 1: To obtain offspring from Horned Hereford cows by breeding them to A. a gene edited, polled Holstein bull, B. a Horned Hereford bull, C. a naturally polled Angus bull and D. the horned Holstein sire of the gene edited, polled bull. (2017-2018) - 100% Obj 2: To evaluate the overall health, development and genetic integrity of the offspring obtained in objective 1. (2017-2020) - 90% All of this data has been collected and we are in the process of writing up the manuscript. Obj 3: To evaluate the dams that carried the calves sired by the genome edited bull and control bulls for evidence of fetal-maternal microchimerism. (2017-2018) - 100% Obj 4: To evaluate the composition of animal products (milk and meat) derived from the objective 1 offspring in comparison to offspring from control bulls. (2018 - 2020) - 60% The five male offspring of the genome-edited bull were euthanized and incinerated in 2019. We collected a sample of chuck arm and sirloin cap from all five bulls. We also collected chuck arm and sirloin cap samples from two bulls with a 25% coefficient of relationship with the genome-edited offspring (controls). These two bulls were slaughtered and entered the food chain as they were control animals and did not contain any "intentional genomic alterations". We used Eurofins Microbiology Laboratories to get proximate analyses (fat, protein, carbohydrate, water, calories and ash), iron and Vitamin B12 content for the chuck arm (n=7), sirloin cap (n=7) and tritip (n=1 genome edited bull). We also analyzed a subset of meat (n=3 offspring of the genome-edited bull, n=1 control) more extensively for important nutritional parameters specific to meat, including eighteen of the twenty amino acids, riboflavin, niacin, Vitamin B6, phosphorus and zinc. These were analyzed for both chuck and sirloin samples from the 4 bulls. The single female offspring of the genome-edited bull was bred to a horned Hereford bull and gave birth in August 2020. Obj 5: To meet with the U.S. Food and Drug Administration (U.S. FDA) to determine what information should be submitted to Center for Veterinary Medicine (CVM) and the appropriate file type to utilize regarding the experimental animals involved in this experiment. (2019 - 2020) - 50% On August 21, 2018 we requested a Type VII Veterinary Master File (VMF) for the production of intentionally genome altered cattle. A meeting was held in December 2018 with the FDA to establish what information was required to support this file and the appropriate file type to submit that data. At the time we were told to open a VMF to submit a request to CVM to allow entry of the male polled offspring into the human food supply. The requested data regarding the offspring was as follows: Description of animals proposed to enter the food supply: i. Species, class, and number of requested investigational animals (state which animals they would like to enter the food supply: (e.g. 5 male calves sired by IGA bull)). ii. Please clarify if the heifer or sire bull will also be part of the request 2. Breeding strategy used to produce the offspring 3. The purpose of the genetic alteration and the intended function 4. Description of the genetic alteration (location in the genome, (impact on protein expression, if any,) intended sequence, etc.) and details of how the genomic alteration was achieved. 5. Comparison of the genetically altered polled sequence to the naturally occurring polled sequence (sequence alignment) 6. Whole Genome Sequencing (WGS) data for: i. the edited parental animal(s) (including information on which animal(s) the data were collected from and the relation of these animal(s) to the offspring) i. the unedited cell line (control) ii. at least 2 of the 5 offspring These data should confirm the alteration as well as validate that there are no unintended modifications to the genome that impact animal safety. 7. Health records for the 5 cattle and comparison to non- edited cattle 8. Provide a nutritional compositional analysis of edible muscle tissues of the investigational animals that will enter food supply including key nutrients. This should be compared with equivalent analysis of a conventional counterpart. Provide information on the methodology used and how the samples were obtained to conduct the meat analysis. Also, information regarding any statistical significance of any observed differences related to natural variation. This analysis may focus on muscle, but if available, can also include data on provide liver, kidney and fat. The Codex Guideline (CAC/CL 68-2008) defines key nutrients are those components in a particular food that may have a substantial impact in the overall diet. They may be major constituents (fats, proteins, carbohydrates as nutrients or enzyme inhibitors as anti-nutrients) or minor compounds (minerals, vitamins). 9. Any concomitant drugs (approved or unapproved) that were used on the animals. 10. Any available information that will help us to conduct the human food safety evaluation (e.g., any feeding studies performed or information from the literature or Recombinetics that you have right-of-reference to that may aid our evaluation). Limit information to those of edited animals at the Celtic allele or relevant (not from conventional breeding). 11. For the bred heifer, if lactating dairy cows are intended to enter the food supply, provide additional information regarding the composition of milk. Data for items 1-7 on the genome edited calves was provided to the FDA (data available BEFORE the animals were killed/had a calf) in December 2018 in a VMF. We subsequently had a conference call with the FDA in May 2019, and we were informed that the only way to get a food use authorization was by opening an Investigational New Animal Drug (INAD), NOT a VMF. The 5 male offspring were subsequently killed, meat was collected to provide the data for point 8 above, nutritional compositional analysis of edible muscle tissues, and then they were incinerated. The female offspring was bred to provide the data for point 11 above, information regarding the composition of milk, and then both she and her calf will also be incinerated. The six cows that gave birth to the genome edited calves were allowed to return to the UC Davis cow herd.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Young, A.E., T.A. Mansour, B.R. McNabb, J.R. Owen, J.F.Trott, C.T. Brown, and A.L. Van Eenennaam, 2020. Comparative evaluation of the phenotype and genome from offspring of a genome edited, hornless bull and controls. Nature Biotechnology 38. 225-232.
DOI: https://doi.org/10.1038/s41587-019-0266-0
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Bishop, T.F., and Van Eenennaam, A.L. 2020 Genome editing approaches to augment livestock breeding programs. J Exp Biol. 2020 Feb 7;223(Pt Suppl 1). pii: jeb207159.
- Type:
Book Chapters
Status:
Published
Year Published:
2018
Citation:
Van Eenennaam, A.L. and A. E. Young. 2018. �Public Perception of Animal Biotechnology, H. Niemann & C. Wrenzycki (ed)�Animal Biotechnology 2. Emerging Breeding Technologies, 275-303
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Van Eenennaam, A.L., Young, A. E. 2018. Public Perception of Animal Biotechnology. Keystone Symposium: Leveraging Genomic Diversity to Promote Animal and Human Health, November 25-29, 2018, Kampala, Uganda
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam, A.L. 2019. Food Animal Species: The Importance of Product Risk-based Regulation of Breeding, American Association Advacement of Science (AAAS) Annual Meeting, February 14-17, 2019, Washington DC
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam, A.L. 2019. The role of genetic improvement on the sustainability of animal agriculture. Midwest Veterinary Conference, February 21-22, 2019, Columbus, OH
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam, A.L. 2019. Understanding genomics, genetic engineering, and gene editing. Midwest Veterinary Conference, February 21-22, 2019, Columbus, OH
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam, A.L. 2019. Genome editing approaches to augmenting livestock breeding programs. JEB 2019 Symposium on `Genome editing for comparative physiology', March 23-26, 2019. Tenuta il Cicalino, Italy
- Type:
Conference Papers and Presentations
Status:
Accepted
Year Published:
2019
Citation:
Van Eenennaam, A. L. Enabling Innovation in Agricultural Breeding Programs: Promises and Prospects. The International Society for Biosafety Research Conference, Tarragona Spain, April 1-4, 2019
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam A. L. Genetics, genomics and transgenesis: Impact in Animal and food production. How biotechnology can vanish world hunger Workshop: Great challenges to science. Campus da USP Fernando Costa , Pirassununga, SP, Brazil, 04/11-13/2019
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Van Eenennaam, A. L. 2019. Genome editing in cattle: Recent developments and prospects. Proceedings of the 2019 Dairy Cattle Reproduction Council Conference. Pittsburgh, PA pp 86-96.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2020
Citation:
Van Eenennaam, A.L. 2020. How Regulatory Factors Influence the Application of Genomics in Animals. Plant and Animal Genome XXVII Conference Abstract #W684
|
Progress 09/01/17 to 08/31/18
Outputs
Target Audience:The target audience includes dairy producers, other researchers, animal scientists, extension specialists, students, veterinarians, industry stakeholders and regulatory representatives. Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?The project has provided opportunities for bioinformatics training and professional development for the Staff Research Associate, who participated in two workshops: UC Davis Bioinformatics Core, Bioinformatics Prerequisites Workshop, March 26-28, 2018, Davis, CA 2018 Data Intensive Biology Summer Research Institute, ANGUS Workshop, July 2-14, 2018, Davis, CA The animals have also served as educational and training examples for a wide variety of visitors, from high school and university students, to media, to visiting scholars, as well as graduate students within our laboratory, and interested members of the general public. How have the results been disseminated to communities of interest?Presentations: Van Eenennaam, A.L. "Innovation in Agricultural Science Lecture: Animal Genome Editing", 2017 National Association of State Departments of Agriculture (NASDA) Annual Meeting, New Orleans, LA, 9/14/2017 Van Eenennaam, A.L. "The Future of Genetic Alteration in Food Animal Production", 50th Annual Conference of the American Association of Bovine Practitioners, Omaha, NE, 9/15/2017 Van Eenennaam, A.L. "Gene Editing: The Polled Phenotype in Dairy Cattle as a Test case for Social License", Breeding for Efficiency 2017 EDGP Symposium, Guelph, Ontario, Canada, 10/16/2017 Van Eenennaam, A.L. "Proposed Regulation of Gene Edited Animals in the U.S.", Netherlands Commission on Genetic Modification (COGEM), Rotterdam, The Netherlands, 10/20/2017 Van Eenennaam, A.L. "Use of Gene Editing in Cattle Breeding", 2017 American Embryo Transfer Association (AETA) and Canadian Embryo Transfer Association (CETA/ACTE) Joint Convention, Orlando, FL, 10/27/2017 Van Eenennaam, A.L. "Will Genome Editing Be Embraced or Eschewed?", North Dakota State University Animal Science Department Graduate Seminar Series, Fargo, ND, 11/7/2017 Van Eenennaam, A.L. "Regulatory oversight of new breeding innovations in the U.S.", TropAgBio2017, Queensland, Australia, 11/19/2017 Van Eenennaam, A.L. "Science communication to obtain social license for use of genome editing in animal breeding programs", The Canadian Agriculture and Agri-Food Genomics Forum, Toronto, Canada, 11/30/2017 Van Eenennaam, A.L. "Innovation in Agricultural Science", 2017 Agribusiness Roundtable, Tempe, AZ, 12/4/2017 Van Eenennaam, A.L. "The Use and Impact of Genetic Technologies in the Dairy Industry", Professional Dairy Producers of Wisconsin (PDPW) Food & Policy Summit, Madison, WI, 12/7/2017 Van Eenennaam, A.L. "Innovation in Agricultural Science?", 2018 Legislative Agriculture Chairs Summit, State Agriculture and Rural Leaders & Council of State Governments, Kansas City, MO 1/6/2018 Van Eenennaam, A.L. "Gene Editing", American Farm Bureau Convention, Nashville, TN, 1/8/2018 Young, A.E., Sonstegard, T.S., Van Eenennaam, A.L. "Evaluation of the Offspring of Genome Edited and Control Bulls", Plant and Animal Genome Conference XXVI, San Diego, CA, 1/16/2018 Van Eenennaam, A.L. "Biotechnology - promise and politics", College of Life Sciences, Brigham Young University, Provo, UT, 1/18/2018 Abstracts: Van Eenennaam, A.L. "The Future of Genetic Alteration in Food Animal Production", 50th Annual Conference of the American Association of Bovine Practitioners, Omaha, NE, 9/15/2017 Van Eenennaam, A.L. "Proposed Regulation of Gene Edited Animals in the U.S.", Netherlands Commission on Genetic Modification (COGEM), Rotterdam, The Netherlands, 10/20/2017 Van Eenennaam, A.L. "Regulatory oversight of new breeding innovations in the U.S.", TropAgBio2017, Queensland, Australia, 11/19/2017 Van Eenennaam, A.L. "Science communication to obtain social license for use of genome editing in animal breeding programs", The Canadian Agriculture and Agri-Food Genomics Forum, Toronto, Canada, 11/30/2017 Young, A.E., Sonstegard, T.S., Van Eenennaam, A.L. "Evaluation of the Offspring of Genome Edited and Control Bulls", Plant and Animal Genome Conference XXVI, San Diego, CA, 1/16/2018 Proceedings: Van Eenennaam, A.L. "The Future of Genetic Alteration in Food Animal Production", 50th Annual Conference of the American Association of Bovine Practitioners, Omaha, NE, 9/15/2017 Press: "This Genetics Company Is Editing Horns Off Milk Cows", Bloomberg Businessweek, 10/12/2017, https://www.bloomberg.com/news/articles/2017-10-12/this-genetics-company-is-editing-horns-off-milk-cows "Making happier animals? Gene editing on the farmyard", Science Friction (ABC radio Australia), 11/17/2017 http://radio.abc.net.au/programitem/perQlnEV5D?play=true "Cattle Geneticist and Active Spokesperson for Ag", Successful Farming at Agriculture.com, 11/23/2017, https://www.agriculture.com/livestock/cattle/cattle-geneticist-and-active-spokesperson-for-ag "Geneticist Alison Van Eenennaam: Genetic engineering could save farm animals from disease", Genetic Literacy Project, 11/29/2017, https://geneticliteracyproject.org/2017/11/29/meet-animal-geneticist-alison-van-eenennaam-one-agricultures-leading-voices-reason/ What do you plan to do during the next reporting period to accomplish the goals?During the next reporting period, the calves will continue to be monitored for horn growth, developmental milestones, and general health parameters. We also expect to complete the bioinformatics analysis on the whole genome sequencing and submit the sequence files to the NCBI Sequence Read Archive. Plans will be made to breed the heifer calf from group A for subsequent milk evaluation and to see if the polled trait is passed to her offspring as expected. The bull calves from group A will be castrated and fed out at the UC Davis feedlot for subsequent meat analysis as detailed in the initial proposal.
Impacts
What was accomplished under these goals?
Objective 1: To obtain offspring from Horned Hereford cows by breeding them to A. a gene edited, polled Holstein bull, B. a Horned Hereford bull, C. a naturally polled Angus bull and D. the horned Holstein sire of the gene edited, polled bull. (2017-2018) - 100% completed Progress: All of the proposed breedings were completed. Outcomes: A. Horned Hereford cows were bred to one of the cloned, gene edited, polled bulls by artificial insemination (AI). Six calves (1 female, 5 males) were born in September, 2017. B. Horned Hereford cows were bred to a horned Hereford bull by AI. Three calves (2 females, 1 male) were born in September, 2017. C. Horned Hereford cows were naturally mated to a naturally-polled Angus bull and a Horned Hereford bull. Two Horned Hereford calves (2 males) and two Angus x Hereford calves (2 females) were born in November, 2017. D. Horned Hereford cows were bred to the sire of the cloned, genetically polled bull used in group a. Three calves (1 female, 2 males) were born in December, 2017. All of the animals are maintained at the UC Davis Animal Science beef barn. Daily care is provided by facility staff. Objective 2: To evaluate the overall health, development and genetic integrity of the offspring obtained in objective 1. (2017-2020) - 33% completed Progress: Calves from all proposed groups were born and their health, development and horn growth have been evaluated regularly and will continue to be evaluated for the remainder of the funding period. Outcomes: The calves were born without incident, with the exception of one Holstein/Hereford control calf from group D (sire of the gene edited polled bull x Horned Hereford dam) that was breech and required veterinary intervention at birth. All calves were monitored and handled by university staff according to standard facility operating procedures. A comprehensive veterinary examination was performed on all of the calves at approximately one week of age by clinicians from the UC Davis William R. Pritchard Veterinary Medical Teaching Hospital Large Animal Clinic. Blood samples were collected by tail venipuncture. Complete blood counts and hematology tests were performed by the clinical laboratory service at the UC Davis William R. Pritchard Veterinary Medical Teaching Hospital. Clinicians also performed manual palpation for horn buds, which were not present in calves from the gene edited or Angus sires, but were present in Hereford control calves and Holstein/Hereford calves. A basic health exam was also performed on all calves and included evaluation of temperature, pulse, respiration, and rumen sounds, all of which were within normal parameters. Males were assessed for the presence of testicles. All bull calves had two descended testicles, with the exception of one of the offspring from the gene edited, polled bull that had one descended testicle and the other above the neck of the scrotum ("high flanker"). DNA was extracted from the blood samples and PCR tested for the polled allele. Results showed that the offspring of the gene edited polled sire are heterozygous for the polled allele, as expected. A second veterinary exam, evaluating the same metrics, was performed at approximately 8 months of age (the calves were on rangeland pasture at 6 months of age, which was the original desired exam time). All calves were reported healthy by the clinicians. The bull calves sired by the gene edited polled bull have developed small scurs, either unilaterally (n=1) or bilaterally (n=4). The heifer calf has no scurs. Scurs, corneous growths that can be of varying sizes and develop in the same area as horns but are not firmly attached to the skull, are a commonly-known occurrence in males heterozygous for polled, so this result is not surprising or outside of normal parameters. Scurs is separate locus from the Celtic horned/polled locus, but the exact causal mutation remains unknown (Wiedemar et al., 2014). None of the offspring of the gene edited, polled bull have developed horns. The purebred control Horned Hereford calves have developed small horns. The Angus x Horned Hereford calves do not show any evidence of horns. At the time of writing, the 8 month exam has not been performed on the section D calves but visual assessment in the field indicates that they are growing horns, as expected. All calves were raised by their horned Hereford dams as a group in a pasture setting. They spent the spring on university-leased rangeland pasture with other cattle from the UC Davis Animal Science beef cattle teaching and research herd. Parentage of each calf was independently verified through testing performed at the UC Davis Veterinary Genetics Laboratory and GeneSeek. DNA samples were also submitted to the QB3 Vincent J. Coates Genomics Sequencing Laboratory at UC Berkeley for next generation library construction and whole genome sequencing. Samples were sequenced on an Illumina HiSeq4000 with paired end 150 bp reads and bioinformatics analysis is currently underway. Objective 3: To evaluate the dams that carried the calves sired by the genome edited bull and control bulls for evidence of fetal-maternal microchimerism. (2017-2018) - 100% completed In order to evaluate potential fetal microchimerism (fetal cells crossing the placental barrier and residing in the mother), blood samples were taken from the dams one month before birth and at weeks 1, 2, 3, 4, and 5 and DNA extracted using the Qiagen DNeasy Blood & Tissue Kit. Quantitative PCR (qPCR) assays for horned, polled, a Y chromosome marker, and a housekeeping gene were performed at the UC Davis School of Veterinary Medicine Real-time PCR Research and Diagnostics Core Facility. Results for all dams showed the presence of the horned allele (as expected). The dam of the heifer calf in group A showed the presence of the horned allele and the polled allele consistent with PCR results for this dam that indicate heterozygosity for the polled allele. None of the dams showed the presence of the Y chromosome marker. The results did not show any transfer of the polled allele from the gene edited polled sire offspring to the dams. Objective 4: To evaluate the composition of animal products (milk and meat) derived from the objective 1 offspring in comparison to offspring from control bulls. (2018 - 2020) - 0% completed This objective will be addressed in Years 2 and 3 when the animals are at appropriate reproductive and production stages, respectively. Objective 5: To meet with the U.S. Food and Drug Administration (U.S. FDA) to determine what information should be submitted to Center for Veterinary Medicine (CVM) and the appropriate file type to utilize regarding the experimental animals involved in this experiment. (2019 - 2020) - 0% completed This objective will be addressed in Year 3 after the data from the previous objectives is collected.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Van Eenennaam, A.L. The Future of Genetic Alteration in Food Animal Production , 50th Annual Conference of the American Association of Bovine Practitioners, Omaha, NE, 9/15/2017
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Van Eenennaam, A.L. Biotechnology - promise and politics , College of Life Sciences, Brigham Young University, Provo, UT, 1/18/2018
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Young, A.E., Sonstegard, T.S., Van Eenennaam, A.L. Evaluation of the Offspring of Genome Edited and Control Bulls , Plant and Animal Genome Conference XXVI, San Diego, CA, 1/16/2018
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2018
Citation:
Van Eenennaam, A.L. Innovation in Agricultural Science? , 2018 Legislative Agriculture Chairs Summit, State Agriculture and Rural Leaders & Council of State Governments, Kansas City, MO 1/6/2018
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Van Eenennaam, A.L. The Use and Impact of Genetic Technologies in the Dairy Industry , Professional Dairy Producers of Wisconsin (PDPW) Food & Policy Summit, Madison, WI, 12/7/2017
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Van Eenennaam, A.L. Innovation in Agricultural Science , 2017 Agribusiness Roundtable, Tempe, AZ, 12/4/2017
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Van Eenennaam, A.L. Science communication to obtain social license for use of genome editing in animal breeding programs , The Canadian Agriculture and Agri-Food Genomics Forum, Toronto, Canada, 11/30/2017
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Van Eenennaam, A.L. Will Genome Editing Be Embraced or Eschewed? , North Dakota State University Animal Science Department Graduate Seminar Series, Fargo, ND, 11/7/2017
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Van Eenennaam, A.L. Use of Gene Editing in Cattle Breeding , 2017 American Embryo Transfer Association (AETA) and Canadian Embryo Transfer Association (CETA/ACTE) Joint Convention, Orlando, FL, 10/27/2017
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Van Eenennaam, A.L. Proposed Regulation of Gene Edited Animals in the U.S. , Netherlands Commission on Genetic Modification (COGEM), Rotterdam, The Netherlands, 10/20/2017
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Van Eenennaam, A.L. Gene Editing: The Polled Phenotype in Dairy Cattle as a Test case for Social License , Breeding for Efficiency 2017 EDGP Symposium, Guelph, Ontario, Canada, 10/16/2017
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Van Eenennaam, A.L. The Future of Genetic Alteration in Food Animal Production , 50th Annual Conference of the American Association of Bovine Practitioners, Omaha, NE, 9/15/2017
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Van Eenennaam, A.L. Innovation in Agricultural Science Lecture: Animal Genome Editing , 2017 National Association of State Departments of Agriculture (NASDA) Annual Meeting, New Orleans, LA, 9/14/2017
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2017
Citation:
Van Eenennaam, A.L. Regulatory oversight of new breeding innovations in the U.S. , TropAgBio2017, Queensland, Australia, 11/19/2017
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